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Biomedical subjects

L A Carlson

Publications and source records attributed to L A Carlson.

At least 19 recordsLinked to original sources

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.

Adult

The association of lipoprotein and hepatic lipase activities with high density lipoprotein subclass levels in men with myocardial infarction at a young age.

The relations between postheparin plasma lipase activities and concentrations of lipoproteins, in particular plasma high density lipoprotein (HDL) subclasses determined by gradient gel electrophoresis, were examined in 39 men who had survived a first myocardial infarction before the age of 45 years and in 20 age-matched control men. Reduced lipoprotein lipase (LPL) and hepatic lipase (HL) activities were found in the patients due to low LPL activity in patients with hypertriglyceridaemia, and low HL activity in those with a normal lipoprotein pattern or hypercholesterolaemia. Considerably lower plasma HDL2b and HDL2a protein concentrations and higher plasma HDL3b and HDL3c protein levels were found in the patients compared with the healthy control subjects. The subgroup of patients with hypertriglyceridaemia accounted for the major proportion of the case control differences for the HDL subspecies. However, significantly lower HDL2b and HDL2a concentrations were seen also among the normotriglyceridaemic patients. Analysis of the correlations between concentrations of HDL subclasses and lipase activities revealed positive associations between LPL and HDL2b and negative associations between HL and HDL2b. For LPL, this relationship was confined to hypertriglyceridaemic and for HL to normotriglyceridaemic subjects. HL was indicated to be positively connected with HDL3b levels, irrespective of lipoprotein pattern, whereas LPL seemed to be unassociated with HDL3b. It is concluded that low LPL and HL activities partly account for the change in HDL subclass distribution observed in patients with myocardial infarction at a young age.

Adult

Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction.

Low density lipoprotein (LDL) from 36 young post-infarction patients was separated by isopycnic density gradient ultracentrifugation to determine the relationships of plasma levels and chemical composition of different LDL subfractions to the global severity and rate of progression of coronary atherosclerosis assessed by angiography. There were marked elevations of the cholesterol and triglyceride concentrations in the very low density lipoprotein (VLDL) fraction, whereas the high density lipoprotein (HDL) cholesterol level was reduced in the patients compared with 70 healthy population-based controls. Plasma total LDL cholesterol and triglyceride concentrations were similar. The distribution of apolipoprotein B along the LDL density range, viz. the LDL particle distribution, was displaced towards the dense LDL region among the patients compared with 14 healthy normolipidaemic controls. A preponderance of dense LDL particles was associated with elevated plasma VLDL triglyceride concentration. The patients had significantly higher plasma concentrations of lipid and protein in dense LDL (d greater than 1.040 kg/l), while no group differences were found in the light LDL (d less than 1.040 kg/l). However, there were no percentage compositional differences in the light or dense LDL between patients and controls. Among all constituents of lipoprotein fractions and subfractions determined, only the plasma level of triglycerides in both light and dense LDL correlated significantly with the angiographic estimates of global severity and rate of progression of coronary atherosclerosis, respectively. On a percentage composition basis, both light and dense LDL tended to be richer in triglycerides in the subjects with a more severe coronary artery disease. Neither VLDL or HDL, nor LDL cholesterol were associated with the angiographic scores, the plasma LDL triglyceride concentration or the triglyceride enrichment of LDL. Although there is ample experimental evidence that triglyceride-enriched LDL predisposes to atherosclerosis, the LDL associations with coronary lesion severity and progression observed in the present study might not reflect a causal mechanism, but merely mirror the atherogenicity of disturbances affecting the metabolism of triglyceride-rich lipoproteins. Prospective studies of larger groups of unselected patients are needed to corroborate these findings.

Apolipoproteins B

The level-of-focal-attention hypothesis in oral reading: influence of strategies on the context specificity of lexical repetition effects.

Two experiments examined the influence of level of focal attention--text or lexical--on benefits from lexical repetition in speeded oral reading of coherent texts and random word lists. Experiment 1 showed that with coherent targets, direction of attention to the text level resulted in benefit only from a previous reading of the same coherent paragraph. However, when attention was directed to the lexical level, equal benefit resulted from a previous reading of either the same coherent paragraph or a scrambled version of the paragraph. Experiment 2 showed that level of focal attention did not influence benefit with scrambled targets. Thus, the linguistic structure of the target is important to repetition benefits and their modulation by attentional strategies.

Analysis of Variance

Studies on the lecithin: cholesterol acyltransferase substrate properties of HDL as determined by its subclass distribution analysed by gradient gel electrophoresis.

In order to study the impact of high-density lipoproteins (HDL) subclasses on the ability of HDL to act as substrate for lecithin: cholesterol acyltransferase (LCAT), we isolated HDL from nine normolipidemic male subjects. The HDL particle size distribution was analysed by gradient gel electrophoresis and the esterification rate of the isolated homologous HDL was compared with a pool of HDL where all the nine subjects took part. It was found that the strongest determinant for HDL cholesterol esterification rate was the inhibitory action of HDL subclass 2B.

Adult

Normalisation of the composition of very low density lipoprotein in hypertriglyceridemia by nicotinic acid.

Large (Sf greater than 100) and small (Sf 100-20) very low density lipoprotein (VLDL) particles were isolated by density gradient ultracentrifugation and characterized chemically in 8 patients with primary hypertriglyceridemia before and after 6 weeks treatment with 4 grammes daily of nicotinic acid (NA). Concomitant changes in high density lipoprotein (HDL) subclass distribution were determined by gradient gel electrophoresis. Small VLDL was subjected to lipolysis in vitro by incubation with bovine lipoprotein lipase before and after NA, and the change in the lipolytic end-product isolated in the low density lipoprotein (LDL) fraction was investigated. Reductions were achieved in the plasma levels of triglycerides, free and esterified cholesterol, phospholipids and proteins in the two VLDL subfractions. In all, the composition of both large and small VLDL particles changed towards potentially less atherogenic particles that were poorer in cholesteryl esters. The HDL cholesterol concentration increased and the HDL protein distribution on gradient gel electrophoresis changed towards larger particles. The mechanism behind the change in cholesterol distribution between VLDL and HDL after NA treatment is unclear, but it could possibly relate to decreased lipid transfer activity. NA reduced the content of apolipoprotein B in both VLDL subclasses and did not decrease the calculated particle size or the number of triglyceride molecules per particle, indicating a reduction of VLDL particle number rather than of particle size. The LDL density fraction isolated after lipolysis in vitro of small VLDL contained less total cholesterol and phospholipids and had a density profile more similar to native LDL after the patients had been treated with NA.

Adult

Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro.

Lipid accumulation in monocyte-originated macrophages in the subendothelial space is an important characteristic of atherosclerotic lesions. Several lines of evidence have indicated that this accumulation occurs as a result of lipid peroxidation. In the present study the ability of probucol to prevent oxidation of low density lipoprotein (LDL) was investigated in 20 hypercholesterolemic individuals taking part in the Probucol Quantitative Regression Swedish Trial (PQRST). The effect of Cu2(+)-induced oxidation of LDL on degradation by macrophages, binding to LDL receptors on fibroblasts and LDL TBARS content was analysed. With LDL isolated from patients on diet alone oxidation led to a 44.3% decreased binding to fibroblasts (P less than 0.001), a ninefold increased uptake in macrophages (P less than 0.001) and a twentyfold increase in TBARS content (P less than 0.001) as compared to native LDL. These values were essentially the same during treatment with cholestyramine alone. However, during treatment with probucol plus cholestyramine exposure of LDL to Cu2+ resulted in an increase in TBARS which was less than 50% (P less than 0.02) of that observed during the other two treatment periods. Furthermore, probucol treatment abolished more than 70% of the decrease in B,E receptor binding to fibroblasts (P less than 0.05) and more than 90% of the increased degradation by macrophages (P less than 0.001) of Cu2+ oxidatively modified LDL.

Aged

Abnormalities of composition and of in vitro lipolysis products of human small very low density lipoproteins in hypertriglyceridemia.

Small (Sf 20-100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 +/- 1.3% (mean +/- SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 less than d less than 1.063 kg/l) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.

Adult

The effects of nicotinic acid treatment on high density lipoprotein particle size subclass levels in hyperlipidaemic subjects.

Twenty-three consecutive hyperlipidaemic patients were treated with 4 g nicotinic acid daily for 6 weeks. The treatment resulted in the expected reduction of serum very low density (VLDL) and low density lipoproteins (LDL) and in the increase of high density lipoproteins (HDL). The cholesterol concentration of the latter fraction rose by 45%. The HDL fraction was isolated by ultracentrifugation and then subjected to gradient gel electrophoresis (gge), in order to determine the HDL particle size distribution, before and after treatment. The increase of HDL was almost exclusively confined to the largest HDL (gge) subclass HDL-2b, the protein content of which rose by 183%. In contrast, there was about a 25% decrease in the concentration of the smallest HDL(gge) subclasses, HDL-3b and HDL-3c. The levels of HDL-2b and VLDL triglycerides showed a significant inverse correlation before, as well as after, treatment. Multiple partial correlation analysis demonstrated, however, that the nicotinic acid induced increase in HDL-2b concentration showed a highly significant inverse correlation to the decrease in LDL cholesterol, but not to the decrease in VLDL triglyceride levels. Recent studies, in particular those regarding the negative correlation between both the degree and progression of coronary atherosclerosis and the HDL-2b concentration in young male myocardial infarct patients, suggest that the profound increase of HDL-2b levels by nicotinic acid treatment in hyperlipidaemic patients might be of considerable importance in the protection of coronary atherosclerosis.

Adult

Influence of human plasma high density lipoproteins from septic patients on different functions of normal human neutrophils.

High Density Lipoproteins (HDL) from three patients with E. coli sepsis contained high, low and no Serum Amyloid Protein (Apo SAA), respectively. Preincubation of neutrophils from healthy persons for half an hour with sepsis HDL as well as normal HDL increased the phagocytosis, the stimulated nitroblue tetrazolium reduction, the chemotaxis and the random migrations of these cells. However, for all these functions, lower values were obtained after incubation with sepsis HDL containing high amounts of apo SAA than with normal HDL. A qualitative change of HDL might thus in part be responsible for the decreased function of neutrophils noted during the acute phase of bacterial infections.

Adult

Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid.

Thirty-one consecutive unselected hyperlipidaemic patients were treated daily with 4 g of nicotinic acid for 6 weeks. The concentrations in serum of lipoprotein Lp(a), and the major lipoprotein classes, were determined before and after the treatment. Nicotinic acid significantly reduced the serum levels of Lp(a) in the whole patient group. Linear regression analysis showed a strong negative relationship between the percentage reduction of Lp(a) and the serum triglyceride level before treatment (r = -0.78), which implied that for patients with a serum triglyceride concentration above 7.5 mmol l-1 there was a rise of Lp(a). The average individual percentage decrease of the concentration of Lp(a) was calculated after the exclusion of four patients who had serum triglyceride levels above 10 mmol l-1. The decrease was 38% with a 95% confidence interval of 28-47%. The absolute decrease of Lp(a) was correlated with the pretreatment levels of Lp(a) (r = 0.91). Within the whole group of patients there was a linear relationship between the percentage decrease of Lp(a) and that of LDL cholesterol (r = 0.88). This latter strong relationship might be due to an inhibition of the synthesis of the protein common to the two lipoproteins, apolipoprotein B.

Adult

Fish-eye disease. A new familial condition with massive corneal opacities and dyslipoproteinaemia.

A man and his three daughters had massive corneal opacities called in their home village "fish-eye disease" because of the resemblance of the eyes to those of boiled fish. The two living daughters had the same dyslipoproteinaemia, characterised by normal serum cholesterol but raised serum triglycerides, raised very-low-density lipoproteins, strikingly high levels of low-density lipoprotein (LDL) triglycerides. LDL contained normal sized as well as abnormally large particles and a 90% reduction in the level of high-density lipoprotein (HDL) cholesterol. Lecithin:cholesterol acyltransferase (LCAT) activity and the percentage of plasma cholesterol esters were normal, with excluded LCAT-deficiency. Normal electrophoretic mobility of HDL as well as other lipoprotein findings excluded Tangier disease. The clinical and laboratory abnormalities in fish-eye disease are atherosclerosis at old age, visual impairment, and dense corneal opacification. Fish-eye disease thus differs both clinically and in its lipoprotein abnormalities from LCAT-deficiency and Tangier disease.

Adolescent